Cytochrome P450 metabolites of arachidonic acid: rapid incorporation and hydration of 14,15-epoxyeicosatrienoic acid in arterial smooth muscle cells
Cytochrome P450 metabolites of arachidonic acid: rapid incorporation and hydration of 14,15-epoxyeicosatrienoic acid in arterial smooth muscle cells
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DOI：
10.1016/s0952-3278(97)90412-9
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发表时间：
1997-10-01
影响因子：
3
通讯作者：
Spector, AA
中科院分区：
文献类型：
--
作者：
Fang, X;Kaduce, TL;Spector, AA
花生四烯酸在细胞色素P450单加氧酶作用下转化为环氧二十碳三烯酸(EETs)。内源性内毒素可引起动脉血管扩张，最近的证据表明它们是内皮衍生的超极化因子。在用血栓素模拟剂收缩的猪冠状动脉中，我们发现暴露于14，15-EET可迅速启动松弛。松弛的幅度缓慢增加，导致持续10分钟以上的反应。培养的猪主动脉平滑肌细胞能迅速摄取[H-3]14，15-EET。3分钟后，中性脂、磷脂酰胆碱和磷脂酰肌醇中出现放射性。细胞还将14，15-EET转化为14，15-二羟基二十碳三烯酸(14，15-DHET)，仅培养1分钟即可在培养液中检测到一些DHET。和14，15-EET一样，14，15-DHET也能松弛收缩的冠状动脉环。这些发现表明，进入磷脂并转化为14，15-DHET的速度可以快到足以调节14，15-EET产生的血管松弛。
Arachidonic acid is converted to epoxyeicosatrienoic acids (EETs) by cytochrome P450 monooxygenases. EETs produce arterial vasodilatation, and recent evidence suggests that they are endothelium-derived hyperpolarizing factors. In porcine coronary arteries contracted with a thromboxane mimetic agent, we find that relaxation is rapidly initiated by exposure to 14,15-EET. The relaxation slowly increases in magnitude, resulting in a response which is sustained for more than 10 min. Cultured porcine aortic smooth muscle cells rapidly take up [H-3]14,15-EET. After 3 min, radioactivity is present in neutral lipids, phosphatidylcholine, and phosphatidylinositol. The cells also convert 14,15-EET to 14,15-dihydroxyeicosatrienoic acid (14,15-DHET), and some DHET is detected in the medium after only 1 min of incubation. Like 14,15-EET, 14,15-DHET produces relaxation of the contracted coronary artery rings. These findings suggest that the incorporation into phospholipids and conversion to 14,15-DHET can occur at a rate that is fast enough to modulate the vasorelaxation produced by 14,15-EET.